Mechanisms and Genetics of Congenital Urogenital Anomalies
- Center for Metabolism and Immunity
Interdisciplinary Research Initiative
2/1/2009 - 1/31/2012
Paul Austin, Helen Liapis, Rakesh Nagarajan, Mark Watson, Keith A. Hruska
Malformations of the kidneys and the urinary system are the most common cause of kidney failure in children, and often have adverse effects on the skeletal (osteoporosis), cardiovascular (hypertension) and hematopoietic (anemia) systems. These defects include absence of kidneys, small kidneys, kidney cysts, multiple kidneys/ureters, dilated ureters, hydronephrosis and reflux. The goal of this project is to delineate molecular and genetic changes associated with kidney and urinary system defects in children. Mice with urinary system defects will be used to systematically identify genes that are abnormally regulated in the diseased urinary system. Genes depicting abnormal expression will be validated in donated human samples from patients with urinary system defects using various molecular and genomic approaches. DNA will be prepared from samples from patients with congenital urogenital anomalies, and coding regions, splice junctions and conserved regions of genes that are critical for urinary system development will be sequenced. Informatics and genomic approaches will be used to identify alterations that may affect the function of these genes. Efforts will be undertaken to prepare high quality DNA targets for genome wide studies to identify multigenic causes of congenital urogenital anomalies. The proposed research will lead to a better understanding of the molecules, genes and mechanisms that lead to congenital urogenital abnormalities, aid in early diagnosis, help devise mechanism–based therapies and strategies to alter the course of associated adverse sequelae.